FRCPath Part 2—Revision Notes on Aspergillus spp.

(Oxford Textbook of Medical Mycology, Ch 10)

1. Genus at a glance

• > 200 species; > 30 human pathogens—among the most ubiquitous environmental moulds; conidia inhaled daily.
• Characteristic aspergillum (asexual conidial head); despite known teleomorphs, the 2012 “one-fungus-one-name” rule retains Aspergillus nomenclature .
• Commercial uses: A. niger → citric-acid & enzyme production; A. oryzae → sake/soy fermentation .

2. Aspergillus Key species, temperatures, toxins & clinical points

Species (complex)	Opt. Temp / Range (°C)	Colony / Microscopy	Major toxin	Salient clinical facts
A. fumigatus	37 / 12-65	Green-blue; columnar uniseriate heads	—	Commonest invasive isolate; ABPA, CPA
A. flavus	37 / 12-48	Green-yellow; radiate uni/bi-seriate	Aflatoxin	Sinusitis, keratitis, aflatoxicosis risk
A. niger	37	Black biseriate heads	—	Otomycosis, onychomycosis
A. terreus	25-40	Beige; biseriate + accessory conidia	Ochratoxin	Intrinsic AmB-R
A. nidulans	37 / 2-48	Green with red-brown cleistothecia	—	CGD infections; AmB-R
A. versicolor	22-26 (opt); ≤40	White→yellow/green; penicillium-like	Sterigmatocystin	Onychomycosis; grows best at room-temp
A. clavatus	37	Long club-shaped vesicle	—	Extrinsic allergic alveolitis (“malt-worker’s lung”)

EORTC definitions

Proven:

• Histologically proven and evidence of tissue damage
• Growth of aspergillus from a sterile site

Probable

• Host factor: neutropenia, transplant, cirrhosis, HIV, chronic lung disease, steroids, infleunza pneumonitis
• Presence in the lower respiratory tract: cytology, microscopy or growth OR GM >0.8 in BALF, >0.5 in serum
• Radiological factors: nodule, air crescent, cavity, wedge/segmental/lobar consolidation, tracehobrachial eschar or ulcer.

Green-yellow radiate, compare to A. fumigatus

Cinnamon colored, columnar

3. Epidemiology & reservoirs

• Conidia in soil, rotting vegetation, damp building materials (wallpaper, concrete, pipe-lagging, carpets, HVAC); hospital construction dust → outbreaks .
• High-risk hosts: prolonged neutropenia, allogeneic-HSCT (~12 %), heart-lung Tx (11 %), CGD, high-dose steroids .
• CPA rising after TB, COPD, sarcoidosis .

4. Pathogenesis (4-step mnemonic I-G-A-T)

1 Inhalation & alveolar deposition

2 Germination when innate immunity fails

3 Angio-invasion → thrombosis, infarction

4 Toxins & hypersensitivity drive allergic / chronic disease

5. Clinical spectrum

Category	Typical entities / notes
Non-invasive	Otomycosis (A. niger), onychomycosis (A. versicolor), allergic fungal rhinosinusitis
Allergic	ABPA (≈16 % asthmatics); EAA by A. clavatus; SAFS
Chronic	CPA continuum: simple aspergilloma → chronic cavitary → fibrosing disease
Invasive	Acute pulmonary IA ± CNS, eye, skin; sinusitis; mortality 50–85 %

6. Diagnosis workflow

1. Direct / culture: septate 45° branching hyphae; Sabouraud agar 48-90 h.
2. Serology & biomarkers:
   1. Aspergillus precipitins (IgG)—best single test for CPA/ABPA support .
   2. Galactomannan ELISA / LFD (false-pos with β-lactams) .
   3. (1→3) β-D-glucan (pan-fungal) .
   4. PCR on blood/BAL; combine with GM for ↑ sensitivity .
3. Imaging: HR-CT halo sign → air-crescent; MRI for CNS/sinus.
4. Histology/BAL/biopsy for EORTC “proven” disease.

7. Antifungal susceptibility & resistance

• Azole-R A. fumigatus increasing in Europe (environmental TR34/L98H, TR46/Y121F/T289A).
• Intrinsic AmB-R: A. terreus, A. nidulans.
• Always request MICs on invasive isolates.

8. Management cheat-sheet

Condition	First-line	Key alternatives / notes
Invasive aspergillosis	Voriconazole	Liposomal AmB; isavuconazole (non-inferior; shortens QT c)
ABPA	Oral steroids ± itraconazole/posaconazole
CPA	Long-term oral triazole; monitor levels
Onychomycosis / Otomycosis	Topical clotrimazole ± oral azole
Surgical	Resection of solitary aspergilloma; debridement of sinus/CNS masses

Supportive: remove colonised lines, taper immunosuppression, give G-CSF if neutropenic.

9. Prognosis & prevention

• IA mortality: 50-60 % (SOT) → 70-85 % (other immunosuppressed). Early targeted therapy improves survival .
• Primary prophylaxis (e.g. posaconazole in AML/allo-HSCT) cuts incidence but monitor for resistance.
• Environmental control: HEPA filtration, positive-pressure rooms, meticulous dust containment during building/refurbishment .

10. High-yield exam pearls

1. Columnar uniseriate head + growth to 65 °C = A. fumigatus.
2. Accessory conidia → think A. terreus (and AmB-R).
3. Galactomannan false-positive with piperacillin-tazobactam or Penicillium.
4. Sterigmatocystin ↔ A. versicolor; ochratoxin ↔ A. terreus; aflatoxin ↔ A. flavus.
5. Report isolates as “A. fumigatus complex” unless molecular ID performed (≥ 40 cryptic species) .
6. Isavuconazole shortens QTc (contrast other azoles).
7. Memorise EORTC/MSG 2008 possible/probable/proven definitions—frequent SAQ.
8. Environmental reservoirs (damp concrete, carpets, HVAC) explain hospital outbreak questions.
9. Room-temperature growth (~25 °C) onychomycosis isolate? Think A. versicolor.